Five decades after medical researchers first started
following the health of mothers and their newborns for an
ambitious longitudinal study, Janet Hardy refuses to let go
of her "babies," who are middle-aged now. Her hope: The
data first gathered when they were in utero will yield
tantalizing clues to the ailments that beset them
today.

Back in the late 1950s it wasn't difficult to
convince 4,000 East Baltimore mothers-to-be to participate
in the Collaborative Perinatal Project (CPP), a national
state-of-the-art research study that tracked the growth and
development of children from their first days in utero
through second grade.

"Many of the people whose kids participated in the study
told us, 'There's not much I can do for other people. This
is something I can do,'" recalls Johns Hopkins' Janet
Hardy, a pioneer in the field of pediatric public health
who directed the Baltimore cohort of the 12-site study at
Hopkins from 1957 until 1976. Nationally, the CPP followed
about 60,000 pregnant women and their 58,000 children.

The hard part was getting the families to come back.

Doctors saw these children at least a half-dozen times at
Hopkins during their seven or eight years in the study,
which was designed to explore the origins of such
neurological and sensory disorders as mental retardation,
cerebral palsy, and learning disorders. At these visits
they were weighed and measured; their hearing, vision,
language, speech, and cognitive development were tested;
and their parents were interviewed about their children's
health and family life. Umbilical cord samples were taken
at delivery, and prior to giving birth, their mothers
visited Johns Hopkins Hospital about once a month for
checkups and to give maternal blood samples. The blood was
used for a serological study being done at the National
Institutes of Health that explored the issue of
maternal-fetal infection.

Being an unpaid participant in the CPP was a huge
commitment, not to mention a "considerable inconvenience,"
says Hardy. Sometimes even the most well-meaning parents in
these lower-middle-class families moved and left no
forwarding address, missed appointments, or otherwise
failed to keep up with the demands of the study.

Hardy refused to let the families slip away. She sent taxis
to their doors to ferry them to doctor's appointments and
always remembered to send birthday and Christmas cards.
"Thank you for coming," Hardy and her staff always told the
women. "Without your help there would be no study."

Due in part to her persistence, the CPP quickly yielded
important insights into preventing brain damage in newborns
with jaundice and preventing such birth defects as
blindness and deafness. The comprehensive workups of
newborns whose mothers were participating in the CPP
created standards for hospitals regarding all newborn care.
Over the next few years, other important findings came
about: CPP researchers learned of the devastating effects
rubella could have during the first and second trimester of
pregnancy, and their findings helped the push for a
vaccine. They found drugs that were unsafe for mothers to
take during pregnancy. And they discovered more about the
problems faced by teenage mothers and low-birth-weight
babies. Their work had a great influence on the decline in
the rate of infant mortality from 29.2 per 1,000 live
births in 1950 to 7.2 in 1999.

Even when the children grew to adulthood, Hardy refused to
let go. Working with colleagues at Hopkins in the late
1980s, she reconnected with several thousand mothers in the
original Baltimore cohort and studied them, their children,
and their grandchildren to learn more about how their
environment influenced their health and development.

Today, at the age of 89, Hardy continues the work she
started decades ago. The original CPP babies are
middle-aged now and are likely suffering from some of the
chronic diseases of midlife: type 2 diabetes, obesity,
heart disease. Some could be schizophrenic or have other
forms of mental illness. So Hardy and the researchers she
inspired are reconnecting with original CPP participants
and are hoping to find answers about when these diseases
actually start.

"People told me this was a dead end," Hardy says of the
CPP study. "They said it wasn't going to work. And these
were some of my friends talking."

"The more we look at complex disorders, the more we
recognize that many adult diseases have their origins in
childhood — many of them go back to in utero
exposures," says Robert Yolken, director of the Stanley
Division of Developmental Neurovirology at Johns Hopkins.
"Dr. Hardy realized this in the 1950s — 30 or 40
years before other people did, and she was very interested
in establishing a study whereby individuals would be
followed literally from in the womb through adulthood."

In the 1950s, maternal and infant mortality and
rates of premature births were high, and many children were
being born with a broad range of neurological and
neurosensory conditions. It was estimated that some 20
million Americans suffered from disabilities, including
cerebral palsy, epilepsy, mental retardation, and defects
of vision, hearing, learning, and communication.

A number of retrospective studies had previously linked
cerebral palsy and mental retardation with dysfunctional
pregnancy, labor, and delivery. Other retrospective
research suggested these problems could be caused by
genetic factors, maternal-fetal viral infection, drugs, and
cigarette smoking. In 1951, two researchers even coined the
phrase "the continuum of reproductive wastage" to refer to
the idea that many pregnancy problems were the cause of
unfavorable outcomes for babies.

Hardy was among those who recognized the value of embarking
on a large, longitudinal study of mothers-to-be and their
children — an ambitious project that would involve
researchers at a dozen major medical centers. "This was
exactly what was needed," Hardy says of the CPP.

The feeling was hardly unanimous. The CPP's length and
breadth — not to mention its collaborative nature and
$100 million price tag — made it controversial. Many
researchers at the time believed that smaller studies
— not one large one — would lead to more
answers. Critics were vocal in their doubting of the CPP's
success. "People told me this was a dead end," Hardy says
of the study, which was funded by the National Institute of
Neurological Diseases and Blindness. "They said it wasn't
going to work. And these were some of my friends
talking."

"It's very expensive to do a study like this, and it's
difficult to carry out in its implementation," says Jonas
Ellenberg, who was chief of the biometry branch of the
National Institute of Neurological Disorders and Stroke,
part of the NIH, during the CPP study. What made the CPP
stand out, he says, was that it allowed for the collection
of lots of data and had a specific, yet still broad, focus.
"Most medical research is driven by hypotheses and would
tend to have a narrow focus," says Ellenberg, currently
associate dean for research program development at the
University of Pennsylvania's School of Medicine.

"The CPP did have hypotheses, but the mechanics for the
design of the study allowed for an extraordinarily broad
access to data that was not hypothesis-driven. The primary
goal of the project was to look at causes of cerebral
palsy, but at the end of the day there was a long list of
medical and clinical outcomes examined that were not talked
about at the beginning of the study."

Hardy looks at the CPP's balance between a narrow and broad
focus as akin to the recipe for soup. "It seems to me a
really good vegetable soup depends on having a basic broth
that provides a sort of starting point," she says. "From
there you can go in all sorts of directions to make the
perfect soup."

The 400-plus specialized publications and presentations
that came out of the CPP are the variations on the basic
vegetable soup. The CPP population and database represents
the broth. "And a very rich broth it was, too," Hardy
adds.

In September 1964, seven years into the CPP, Hardy
and her team began seeing a number of very sick, very
strange looking babies being born to participating mothers.
Their skin was yellow from jaundice and dotted with purple
lesions, their livers and spleens were enlarged, and their
bodies were puffy and swollen with fluid.

Janet Hardy (left) with Anne Duggan and William Eaton,
two of the Hopkins researchers who will carry on her
work. Photo by
Keith Weller

The cause was congenital rubella, a virus their mothers had
experienced early in pregnancy. Hardy and her team were
aware of the virus — thousands of rubella babies were
being born at U.S. hospitals in 1964 and 1965. But the
outbreak among Baltimore newborns in the CPP gave the
researchers a perfect opportunity not only to study rubella
but also to document how an infection spreads from mother
to fetus. Working with John L. Sever at the NIH, Hardy and
her team were able to show — using sera samples and
viral cultures they had taken for the CPP — how
rubella is transferred in utero.

"This was one of the really strong parts of the CPP," Hardy
says. "We had all kinds of mothers and newborns — we
were able to identify mothers who had antibodies to rubella
and mothers who didn't and we had babies in the nursery
with clinical symptoms. Using the data we had, we were not
only able to identify rubella but other infectious
agents."

The nationwide rubella epidemic would leave an estimated
20,000 to 30,000 children with disabilities that ranged
from blindness and deafness to severe mental retardation.
But the Hopkins CPP team's contributions to understanding
how the virus spread helped educate health care providers
about the disease and assisted in the effort to get federal
funding to support the introduction of a rubella
vaccine.

When the CPP ended in 1976, researchers at other
institutions moved on to new projects and new subjects. But
Hardy could not. She was too curious and had too many
questions about how a child's environment influences his or
her life.

During the CPP, Hardy had observed that women who had their
first babies as teens were at higher risk for pregnancy
complications than older mothers, and that their surviving
children faced substantial health and developmental risks.
What could be done to help these women and children and
others like them? And what kind of adults would the CPP
babies become: Would they go to college or have babies
young? Would they become self-sufficient or live on public
assistance?

She didn't know the answers. But she knew where to find
them.

When Baltimore CPP families completed the study, Hardy and
her staff would always present them with a certificate of
participation. They'd also ask for a way to get in touch in
the future. "We never believed it was over," Hardy says of
the CPP study. "Each step was always leading to the
next."

It's not easy to have an infant. It's even harder to
have an infant when you are not so far from childhood
yourself.

"What struck me during the CPP was that we had known for
years that children born to elderly mothers had problems,
but there had been no major focus on young mothers," Hardy
says. "When we looked at our data, we realized that mothers
under the age of 18 were at extremely high risk from
pregnancy loss, their children died at a higher proportion
in the first year of life, and their children had lower IQs
and more developmental problems. We had the information
that the situation was bad, so we wanted to do something
about it."

Janet Hardy
"An ExtraordinaryRole Model"

Born: January 14, 1916

Education: BS, University of British Columbia
(1937); MDCM from McGill University (1941). Decided on a
career in medicine after her father, an internist, once
told her, "No daughter of mine is ever going to be a
physician."

Career Highlights: Served on the pediatric house
staff at Johns Hopkins Hospital (1942-1945), where she was
charged with developing the hospital's first neonatology
ward; consultant to state of Maryland Health Department
(1946-1950), where she helped develop a statewide transport
system for premature and at-risk newborn infants; worked
for Baltimore City Health Department (1951-1957), first as
director of maternal and child health, ultimately as
assistant commissioner of health for preventive medicine;
director of Johns Hopkins Collaborative Perinatal Study
(1957-1976); director of the Office of Continuing Medical
Education at JHMI (1974-1981); director of Johns Hopkins
Adolescent Pregnancy Programs (1975-1985); director of
Johns Hopkins Children and Youth Programs (1982-1985);
fifth woman to achieve rank of full professor on the
Hopkins medical faculty.

Family: Married to Johns Hopkins associate professor
Paul H. Hardy for 66 years; has two children and three
grandchildren. The couple reared their family on a 35-acre
farm in Glen Arm, Maryland, where she raised horses, kept a
garden, and canned her own jams and vegetables. Says Anne
Duggan: "She's an extraordinary role model for how you can
really have it all. She's an incredible researcher, wife,
mother, grandmother, homemaker, gardener. And she has
always made it look effortless."

Working with the late Theodore King, former chair of
Hopkins'
Department of Gynecology and
Obstetrics, and other colleagues, Hardy put together
the Johns Hopkins Adolescent Pregnancy and Parenting
Programs in 1976. The project looked at teaching parenting
skills to teens and teaching and evaluating pregnancy
prevention methods. "It was a special clinical program that
was very supportive and focused on health and parenting
education," Hardy recalls.

Several years later, Hardy became aware of new research by
Laurie Schwab Zabin, a professor of
population and family health sciences at the Bloomberg
School of Public Health, that showed that pregnancy
prevention efforts needed to reach teenagers earlier than
previously thought. The two worked with city children's
advocate Rosalie Streett to develop the Hopkins Pregnancy
Prevention Program. The innovative school-linked program
was implemented at a Baltimore City high school and a
junior high. The program, which blended social support,
education, and access to birth control for young men and
women, succeeded in decreasing the pregnancy rate among
participants by 30 percent while pregnancy rates at schools
without the program grew 58 percent.

Zabin calls Hardy a dedicated, dogged researcher, someone
who not only has curiosity but also has the ability to get
the right people together for a project and find the
funding to make it work. "When she decided something was
going to be done, she totally threw herself into it, picked
very carefully who she was going to do it with, and did
it," Zabin says. "She's always been a person who saw what
the next step could be."

Then there was the question of how the CPP participants,
their children, and grandchildren were faring. After
approximately 25 years since her last contact with CPP
mothers and children, Hardy decided it was time for a
follow-up. In 1988, together with the late Sam Shapiro of
the Bloomberg School's
Department of Health Policy and Management, Hardy
reconnected with a random sample of 2,694 CPP participants
for the Pathways to Adulthood Study. The goal: to see how
their environment and health had influenced their
development.

"Clearly the question was what had happened to the mothers
and the children, and why did it happen," Hardy says.
Because of the fine relationship her CPP staff had with
participants, Hardy had little trouble finding the
children, who were now between the ages of 27 and 33.

There was the baby who, though tiny and brain
damaged at birth, went on to lead an independent life and
have a family. There was the girl with the high IQ who won
a full scholarship to college. There were babies who grew
up to be doctors, lawyers, and small business owners, and
babies who grew up to continue the poverty cycle, live on
welfare, and go to prison.

"It was amazing to see as the children developed and the
families made their way in life," Hardy says. "So many of
them turned out to be successful."

Hardy's follow-up study found that living with both
parents, remaining free from poverty, and good behavior in
and out of school were all predictors of successful adult
lives among this inner-city population, which was largely
African American. She also found a strong link between a
woman's age when she first gives birth and how her children
do later on in life. Those born to mothers in their late
20s were more likely to get high school diplomas, stay off
public assistance, and avoid teenage pregnancies in their
own lives than were the children of teenage mothers.

It was more than curiosity that brought Hardy back to the
CPP data several years ago. "We were beginning to hear of
findings, particularly from a researcher named David Barker
in England, that there was definitive evidence between
perinatal factors and chronic diseases such as diabetes,
heart disease, and hypertension, yet there were very few
databases that included detailed prospective data from the
mother's pregnancy through the children's development to
adulthood," Hardy says. The original CPP data, which
included a collection of 60,000 frozen sera samples, could
be a goldmine.

Now Hardy just needed Hopkins researchers who were
interested in the next step — following the
participants to middle age. Says Duggan: "[Janet] realized
the incredible value [of continuing] to follow the cohort
but [knew] it was never going to happen unless she took
action to pass along to a next generation of researchers
what she had done."

William Eaton, chair of the
Department of Mental Health at the Bloomberg School of
Public Health, has been interested in life course studies
for most of his career and immediately saw the value of
continuing the CPP. "We have studied thousands of
generations of fruit flies . . . and hundreds of
generations of rodents, but [there's not been] a single
intensive study of even one generation of humans," he says.
"Following up on the CPP is one of the first opportunities
we have to do that."

"We have studied hundreds of generations of rodents ...
but [there's not been] a single intensive study of even one
generation of humans." —William
Eaton

Along with Duggan, Eaton has been spearheading the effort
to embark on the latest follow-up. They've just completed a
pilot study proving that they are able to reconnect with
participants, and they are still finding research
specialists to sign on to the project and plan to apply for
funding in February.

Yolken, the Hopkins neurovirologist, had already used sera
samples from the CPP for some of his work, including a
recent study that found an increased incidence in
schizophrenia among adults whose mothers had herpes simplex
virus II when they were pregnant. He signed on to the
follow-up of the now middle-aged "CPP babies" because he
knows the richness of the data that was already available
and he's eager to see where new data might lead. "The
collaborative perinatal study was probably the best study
of its kind that's ever been done," Yolken says. "I don't
think any study since then has really characterized that
many children and also collected prenatal and cord blood
samples that were stored in an archive."

And then there's the opportunity of working with Hardy,
whom Yolken calls an "oral historian" of the CPP. "Dr.
Hardy has been an incredible resource," he says. "She has
an incredible memory and anytime I've had questions about
what a particular variable means I simply ask her. I can
get information from her that's not documented, or if it is
documented I haven't been able to find it from other
sources."

Hardy is thrilled that Eaton, Duggan, and other researchers
at Hopkins have agreed to carry on her work. "I'm just so
fortunate to have it in better hands than mine," she says.
"I no longer have any feeling of ownership. I guess it's
analogous to having one's children grow up."

And yet, even Hardy doubts she will ever really be able to
leave the CPP behind. She's curious about what the new
findings might be and professes a desire to see the
completion of the most recent follow-up. "They have a
wonderful opportunity to do a quick and dirty study to
answer some of the current hypotheses about the development
of midlife chronic disease," Hardy says. "Does it start in
utero? If so, why? And what are the mediating factors along
the way? You have a confluence of the database, a
population, and rather urgent scientific questions. For my
money, that makes for a very exciting situation."

However, Hardy admits she has one regret. "I only wish I
could see it done," she says.

Eaton considers Hardy's words for a moment and laughs.
"That's a lot of crap," he says. "She's just talking. She
is going to be here."